PREVENTING RESTENOSIS FOLLOWING PTCA / 药物分析学报

ABSTRACT

Whether InfusaSleeve(IS) catheter can deliver antisense oligodeoxynucleotide (ODNs) following arterial denuation is unknown. We evaluate the feasibility of local endoluminal delivery of C-myc ODNs to the site of arterial denudation by using IS catheter and to determine the biological importance of these effects. IS catheter was introduced into right side of iliac artery of 21 rabbits after angioplasty of iliac artery. Animals were randomized to the control group (n＝6) receiving saline injection and the treated group receiving c-myc antisense (n＝15, 1 mg ODNs per vessel). In two weeks and 40 days following the operation, angiography was performed. Morphometric analyses were carried out in balloon-denuded iliac arteries. The expression of c-myc protein was detected by using a mouse monoclonal antibody to c-myc. Morphometric analyses carried out at 40 days after transcatheter c-myc antisense oligomer administration. The results showed that maximal neointimal area was reduced from 7.66±3.7(×105 μm2) in the control group (n＝6) to 4.04±1.02(×105 μm2) in the antisense treated group (n＝6, P＜0.05). These changes in vascular remodeling following denuding injury resulted in an increase in residual luman from 20～50% in the control group to 70～90% in the antisense-treated group. C-myc protein expression was virtually undetectable at baseline in locally ODNs-delivered arteries and detectable in control denuded arteries. The results show that: ①Single IS transcatheter administration allowed endoluminal delivery of ODNs to the site of arterial injury; ② c-myc antisense oligomer reduced the formation of neointime in denuded arteries, implying a therapeutic potential of this approach.